ABSTRACT
Starting from 4-amino-antipyrine, six new compounds were synthesized and characterized. The new compounds contain moieties with particular properties, such are ionophore (benzo-15-crown-5), fluorescent (nitrobenzofurazan), stable free radical (nitroxide), or other types of biological active residues, like nitroderivatives, antipyrine or isoniazid residues. They were fully characterized by appropriate means ((1)H and (13)C NMR, IR, UV-Vis, fluorescence, EPR, elemental analysis) and some of their biological properties were evaluated. Hydrophobicity (R(M0), log P), total antioxidant capacity (TAC), and antimicrobial properties are also presented and discussed.
Subject(s)
Anti-Bacterial Agents/chemical synthesis , Antioxidants/chemical synthesis , Antipyrine/analogs & derivatives , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Pyrazolones/chemical synthesis , Anti-Bacterial Agents/pharmacology , Antioxidants/pharmacology , Antipyrine/chemical synthesis , Antipyrine/pharmacology , Apoptosis/drug effects , Cell Cycle/drug effects , Cell Line, Tumor , Cell Survival/drug effects , Gram-Negative Bacteria/growth & development , Gram-Positive Bacteria/growth & development , Humans , Hydrophobic and Hydrophilic Interactions , Magnetic Resonance Spectroscopy , Pyrazolones/pharmacology , Spectrometry, Fluorescence , Structure-Activity RelationshipABSTRACT
The 3+2 cycloaddition reaction of 1-(4-phenylphenacyl)-1,10-phenanthrolinium ylide 4 with activated alkynes gave pyrrolo[1,2- 4a][1,10]phenanthrolines 6a-d. The "one pot" synthesis of 6a,b,d from 4, activated alkenes, Et(3)N and tetrakis-pyridine cobalt (II) dichromate (TPCD) is described. The helical chirality of pyrrolophenanthrolines 6b-d was put in evidence by NMR spectroscopy.
Subject(s)
Alkynes/chemistry , Cycloparaffins/chemistry , Heterocyclic Compounds/chemical synthesis , Catalysis , Cyclization , Models, Biological , Phenanthrolines/chemistry , StereoisomerismABSTRACT
Important physiological and physio-pathological functions are played by several carbonic anhydrase (CA, EC 4.2.1.1) isozymes, which are strongly inhibited by aromatic and heterocyclic sulfonamides. Here we report several new types of such sulfonamides, incorporating furan-, thiophene- and pyrrole-carboxamide moieties in their molecules. Some of these compounds showed very good CA II and CA IV inhibitory properties. with affinities for the enzymes in the low nanomolar range. Due to their relatively low water solubility, some of the most active CA II inhibitors reported here have been formulated as aqueous suspension for topical administration as antiglaucoma agents. in normotensive and glaucomatous rabbits. The derivatives incorporating furan- and pyrrole-carboxamide moieties (but not the corresponding thiophene-substituted derivatives), showed effective and long-lasting intraocular pressure (IOP) lowering both in normotensive as well as glaucomatous animals, with potencies superior to dorzolamide and brinzolamide, the two available topically acting sulfonamide drugs. This is the first example of non-water soluble sulfonamides that significantly lower IOP, being thus similar with the recently introduced drug brinzolamide, which belongs to a completely different chemical family of antiglaucoma sulfonamides.